Purdy finished with 295 yards, five touchdowns, and one interception on 25-of-34 passing.
49ers running back Christian McCaffrey finished the game with a total of 146 yards (117 rushing) and two touchdowns. He averaged 5.6 yards per carry on 21 attempts.
Colts' Philip Rivers finished with 277 yards, two touchdowns, and one interception on 23-of-35 passing, leaving him with two more games left to seek his first win in the NFL since January 3, 2021 against the Jacksonville Jaguars.
Full game recap + highlights
First half
Rivers led the Colts down the field on the first drive of the game, ending with a 20-yard touchdown pass.
Pierce was only thee years old when Rivers was drafted in 2004.
San Fran followed in fashion with a score of their own on their first drive of the night.
Purdy found Demarcus Robinson in the end zone to cap off a six-play, 69 yard drive, tying it all up 7-7.
The touchdown marked Robinson's first as a 49ers.
On the ensuing kickoff, the 49ers would get the ball back after forcing a fumble on return man Ameer Abdullah.
It didn't take long for the for the 49ers to find the end zone again, as Purdy found running back McCaffrey for his 15th total touchdown on the season.
But the Colts wouldn't go away as they ended up tying the game with yet another Rivers-to-Pierce connection in the end zone to tie it up 14-14.
The touchdown marked the first multi-touchdown game for Pierce in his current four-year career.
49ers responded with a touchdown their third straight touchdown on their third drive of the game.
This time, Purdy found veteran tight end George Kittle in the back of the end zone to take the 21-14 lead.
Both teams would exchange field goals each before heading into the locker room for halftime with the 49ers ahead 24-17.
With three seconds left in the half, Eddy Piniero attempted a 64-yard field goal, which would've been a career-high, but bounced off the crossbar for his first missed field goal of the entire season.
Both teams would score on seven of the game's 10 drives of the first half. San Fran outgained Indy 250-194 with 16 first downs to the Colts' 11.
Second half
To open up the second half, the 49ers did what they had been doing all night beforehand - score touchdowns.
Purdy connected with wide receiver Jauan Jennings for his fourth passing touchdown on the night, Jenning's eighth on the season.
Both teams would exchange field goals after the touchdown to make it 34-20 before heading into the fourth quarter.
The Colts would cut the game to one-score with 12:41 left to go in the game after Jonathan Taylor scored his 20th total touchdowns (17th rushing) of the season to make it a 34-27 game.
Making, it once again, four straight combined drives that would end in a score between both teams. At that point in the game, either team would score on 11 of the game's 14 drives.
Purdy would continue to tear up the Colts' secondary all night long after he earned his fifth touchdown pass of the game with just over five minutes left in the game to put San Fran up 41-27.
The same drive saw McCaffrey turn on the jets for 24-yard run, which would be his biggest of the entire 2025 season.
What would look like some hope for the Colts after defensive back Cam Bynum picked off Purdy, the 49ers would respond with one of their own just a three plays plays later - except they would return it for six.
Linebacker Dee Winters would take it to the house to put the 49ers up 48-27, ensuring a definitive victory.
The 49ers improved to 11-4 on the season, making the NFC West divisional race that much more interesting, while the Colts' playoff window is almost all but shut.
